P53和SOX2蛋白表达可预测食管腺癌对新辅助放化疗的反应。

P53 and SOX2 Protein Expression Predicts Esophageal Adenocarcinoma in Response to Neoadjuvant Chemoradiotherapy.

作者信息

van Olphen Sophie H, Biermann Katharina, Shapiro Joel, Wijnhoven Bas P L, Toxopeus Eelke L A, van der Gaast Ate, Stoop Hans A, van Lanschot Jan J B, Spaander Manon C W, Bruno Marco J, Looijenga Leendert H J

机构信息

*Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, The Netherlands †Department of Pathology, Erasmus University Medical Center Rotterdam, The Netherlands ‡Department of Surgery, Erasmus University Medical Center Rotterdam, The Netherlands §Department of Medical Oncology, Erasmus University Medical Center Rotterdam, The Netherlands.

出版信息

Ann Surg. 2017 Feb;265(2):347-355. doi: 10.1097/SLA.0000000000001625.

DOI:10.1097/SLA.0000000000001625

PMID:28059963

Abstract

OBJECTIVE

The aim of the study was to investigate the association between p53, SOX2, and CD44 protein expression and tumor response, and to validate potential predictive biomarker(s) in an independent cohort.

BACKGROUND

Neoadjuvant chemoradiotherapy (nCRT) followed by surgery has become a standard of care for esophageal adenocarcinoma (EAC). However, the response to nCRT is highly variable among patients.

METHODS

EAC patients who underwent nCRT and surgery, between January 2003 and December 2014 at the Erasmus University Medical Center, were included and divided into a primary (n = 77) and a validation cohort (n = 70). P53, SOX2, and CD44 expression was detected by immunohistochemistry in pretreatment tumor biopsies, and scored independently by 2 investigators. Response to nCRT was assessed based on tumor regression grade (TRG) in the resection specimen.

RESULTS

Forty-one (53%) patients in the primary cohort and 33 (47%) patients in the validation cohort showed major response (TRG1 or TRG2) in the resection specimen. Aberrant p53 and absence of SOX2 were associated with major response in the primary cohort: adjusted odds ratio (OR) 6.3 [95% confidence interval (CI), 1.3-30.1) and adjusted OR 4.1 (95% CI, 1.4-12.4), respectively. The same was true for the validation cohort (p53: adjusted OR 8.6; 95% CI, 0.93-80.9 and SOX2: adjusted OR 6.1; 95% CI, 1.6-23.4). The highest probability of a major response was seen in patients with concurrent aberrant p53 and absence of SOX2 expression, with an OR of 6.7 (95% CI, 2.1-21.4) and 6.2 (95% CI, 1.8-21.2) in the primary and validation cohort.

CONCLUSIONS

Pattern of p53 and particularly SOX2 protein expression in EAC predicts response to nCRT. These biomarkers may help to individualize treatment in EAC patients.

摘要

目的

本研究旨在调查p53、SOX2和CD44蛋白表达与肿瘤反应之间的关联，并在一个独立队列中验证潜在的预测生物标志物。

背景

新辅助放化疗（nCRT）后行手术已成为食管腺癌（EAC）的标准治疗方案。然而，患者对nCRT的反应差异很大。

方法

纳入2003年1月至2014年12月在伊拉斯谟大学医学中心接受nCRT和手术的EAC患者，并分为一个主要队列（n = 77）和一个验证队列（n = 70）。通过免疫组织化学在治疗前肿瘤活检中检测p53、SOX2和CD44的表达，并由2名研究人员独立评分。根据切除标本中的肿瘤退缩分级（TRG）评估对nCRT的反应。

结果

主要队列中的41名（53%）患者和验证队列中的33名（47%）患者在切除标本中显示出主要反应（TRG1或TRG2）。p53异常和SOX2缺失与主要队列中的主要反应相关：调整后的比值比（OR）分别为6.3 [95%置信区间（CI），1.3 - 30.1]和调整后的OR 4.1（95% CI，1.4 - 12.4）。验证队列也是如此（p53：调整后的OR 8.6；95% CI，0.93 - 80.9；SOX2：调整后的OR 6.1；95% CI，1.6 - 23.4）。在p53异常且无SOX2表达的患者中观察到主要反应的概率最高，主要队列和验证队列中的OR分别为6.7（95% CI，2.1 - 21.4）和6.2（95% CI，1.8 - 21.2）。